Within recent years there has been considerable interest in the role of the ingestion of polyunsaturated fatty acids in the prevention or treatment of arthritis, soft tissue inflammation and cardiovascular disease. This interest has arisen from the observation that Greenland Eskimos, on a traditional native diet, showed disease patterns quite different from age-matched individuals in Europe and North America. The most striking differences observed were the reduced incidence of heart disease, asthma, psoriasis and rheumatoid arthritis in Eskimo populations (1).
Examination of the Eskimo dietary lipid intake showed elevated levels of highly unsaturated fatty acids (HUFAs) arising from their high consumption of fish and marine, mammals. Subsequent clinical trials initiated by Kremer and co-workers (2) have demonstrated that the manipulation of the dietary intake of fatty acids to include higher levels of HUFAs in caucasian patients with rheumatoid arthritis could decrease the symptoms of arthritis.
The mechanism of action of this dietary intervention was considered, in part, to be dependent on the ability of the HUFAs to act as competitive substrates for enzymes involved in prostaglandin and leukotriene biosynthesis. Eicosapentaenoic acid (EPA) (20:5, n=3) and docosahexaenoic acid (22:6, n=3) are the principle long chain unsaturated fatty acid triglycerides in fish oil. EPA incorporated into cell membranes may be converted via the cyclooxygenase enzymes into the regulant prostaglandins, thromboxanes and prostacyclins of the 3-series (2-5) whereas PGE.sub.2 produced from arachidonic acid precursors was a potent mediator of inflammation. EPA metabolised via the lipoxygenase pathway produces leukotriene B5 (2-5). Leukotriene B5 is 10-30 times less potent an inflammogen than leukotriene B4 which is normally produced from arachidonic acid. Thus dietary fish oil supplementation may support endogenous anti-inflammatory activity by modifying the production of harmful mediators within the animal's tissues.
An alternative pathway of unsaturated fatty acid metabolism is via the C18-triunsaturated fatty acids, gamma and alpha linolenic acid. While the alpha isomer (9, 12, 15 octadecatrienoic acid) may be shunted into the prostaglandin E.sub.3 pathway, gamma linolenic acid (6, 9, 12 octadecatrienoic acid) is converted into dihomo-gamma-linolenic acid (DGLA) which is the biosynthetic precursor of the the anti-inflammatory prostaglandin E.sub.1 (PGE.sub.1) (6).
Evening primrose oil is also a rich source of gamma linolenic acid (7) and has been demonstrated to suppress chronic adjuvant induced polyarthritis in the rat (6) as well as in patients with rheumatoid arthritis (8).
There have been limited studies on the effects of administering these C18 unsaturated fatty acids topically for the treatment of inflammatory conditions.
In PCT/AU89/00555 (WO 90/07331) it is disclosed that linseed oil and other plant derived oils, which contain alpha linolenic acid, when dispersed in an appropriate solvent or thinner display topical anti-inflammatory activity. The specification goes on to disclose that the activity of this composition is thought to arise due to its alpha linolenic acid (9, 15, 15, octadecatrienoic acid) content. Suitable thinners, which in the context of the application mean compounds for increasing the transdermal transport of linseed oil, are said to be mineral or distilled turpentine, methyl,ethyl- and isopropylsalicylate esters, eucalyptol (cineole) tea tree oil and oil of wintergreen. These thinners in combination with the linseed oil are stated to exhibit synergism and a surprising anti-inflammatory effect.